In situ nail unit melanoma: epidemiological and clinic-pathologic features with conservative treatment and long-term follow-up.

BACKGROUND: Nail unit melanoma (NUM) is a rare melanoma variant, usually associated with a poor prognosis because of a delayed diagnosis. Few data are available concerning the management and long-term outcome of in situ NUM. OBJECTIVE: To use a large cohort to provide comprehensive patient data and long-term follow-up information. This will serve to investigate distinctive epidemiological, clinical and histological features of in situ NUM. To report treatment modalities, assess conservative surgery and evaluate its long-term safety. METHODS: Patients with confirmed diagnosis of in situ NUM were retrospectively reviewed. Demographics, clinical presentation, therapeutic data and follow-up were analysed. RESULTS: Sixty-three cases of in situ NUM were identified as follows: 44 were women (70%), with a mean age of 51 years. The mean duration of symptoms prior to consultation was 4.3 years [range 3 months-28 years]. Clinically, with 58 cases, i.e. (92%) longitudinal melanonychia was the most common clinical presentation. The thumb was the most affected digit, being afflicted in 28 cases: 44%. Medical history found a widening and/or recent darkening of the melanonychia in 46 cases (82%). The treatment consisted of, respectively, 56 En bloc excisions of the nail apparatus 89% of the patients we studied, and seven amputations of the distal phalanx. During the follow-up period (mean: 10 years), two patients presented in situ recurrences. CONCLUSION: The recognition of a NUM at an in situ stage allows early treatment and curing of this tumour. At this early stage, a 'functional surgery' is a rational approach with an excellent oncologic safety.

CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts.

BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-κB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-κB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-κB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. RESULTS: Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. CONCLUSIONS: Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

[Psoriasis: physiopathology and immunogenetics]. / Le psoriasis: physiopathologie et immunogénétique.

Psoriasis is a multifactorial disease that involves genetic, immunological and environmental factors. During the last decade, several studies by genome scan on families or cases/controls helped to highlight more than ten loci "PSORS" located on different chromosomes and containing several candidate genes. Psoriasis appears as a genetic disease that follows the mixed model with the involvement of a major gene (PSORS1) and a set of minor genes with a variable penetrance depending on the locus. Genetic data have focused on the involvement of the immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis is an immunological disease involving the response profiles TH1 and TH17. Much remains to be done to better elucidate the mechanisms involved in the genesis of psoriatic lesions to find new therapeutic targets.

Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families.

BACKGROUND: Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region. OBJECTIVES: To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia. METHODS: Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome. RESULTS: No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A. CONCLUSIONS: Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.

Acute generalized exanthematous pustulosis induced by the essential oil of Pistacia lentiscus.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon pustular eruption characterized by small nonfollicular pustules on an erythematous background, sometimes associated with fever and neutrophilia. Over 90% of cases are drug-induced; however, it can be caused in rare cases by other agents. We report two cases of AGEP secondary to ingestion of Pistacia lentiscus essential oil, the first two such cases to our knowledge. The cutaneous morphology, disease course and histological findings were consistent with a definite diagnosis of AGEP, based on the criteria of the EuroSCAR study group. These two cases highlight the need to consider herbal extracts as a potential rare cause of AGEP and to ensure the safety of herbal medicines.

[Extensive Dowling-Degos disease following long term PUVA therapy]. / Maladie de Dowling-Degos étendue après PUVA thérapie prolongée.

BACKGROUND: Dowling-Degos disease is a rare and benign inherited dermatosis. PATIENTS AND METHODS: A 53-year-old woman presented with generalized histologically confirmed Dowling-Degos disease revealed 8 years after psoralen photochemotherapy (PUVA) for psoriasis. This presentation was special in terms of its considerable spread as well as the absence of comedone-like and punctate scars. DISCUSSION: Dowling-Degos disease is a reticulate pigmentary disorder of the flexures associating prominent comedone-like lesions and pitted scars. Diagnosis is based on clinical and histopathological examination, which allows this entity to be differentiated from other reticulate pigmentary disorders. A literature review failed to provide any indication that PUVA therapy either aggravates or reveals Dowling-Degos disease, a finding which we feel merits mention.

Nail lichen planus: epidemiological, clinical, pathological, therapeutic and prognosis study of 67 cases.

BACKGROUND: Lichen planus limited to the nail is uncommon, and information about its long-term prognosis is lacking. OBJECTIVES: We attempted to review the epidemiological, clinical and histological features, the response to treatment and the follow-up of a large series of patients with nail lichen planus (NLP). METHODS: We searched for the records of all patients with a clinical and histopathological diagnosis of isolated NLP apart from January 1997 to December 2008. The patients presented during this period and followed until December 2009 in the consultation for nail disorder were reviewed in detail. RESULTS: Data on 67 patients were collected, with an average age of 47 years (6-78 years). A male preponderance was observed (64%). The mean duration of the disease was about 38 months. Fingernails were the site of involvement in 94% of cases. Matrix involvement was observed in 91% of cases. A total of 120 specimen's biopsy were taken and was contributory in 90% of cases. Two specimens biopsy were practiced in 70.15% of patients. Systemic corticosteroids were used in 46 patients, and associated in 20 cases to intralesional corticosteroids. CONCLUSIONS: Our findings indicate that if NLP is correctly diagnosed and appropriately treated. Nail biopsy is proven to be a relatively simple, safe and useful procedure with a minimal scarring risk. Long-term observation indicates that the prognosis of NLP is poor with high rate of relapses, with permanent damage to the nail unit.

Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo.

Auto-reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitiligo but the mechanism underlying the loss of self-tolerance is unknown. A deregulation of regulatory T-cell biology has recently been suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in seven of 15 cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms, suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was further corroborated by the significant increase of Forkhead box P3 expression in the vitiliginous skin of patients. Our data support the involvement of a functional defect of peripheral regulatory T cells in the pathogenesis of vitiligo and open new possibilities to advance therapeutic approaches.

Angiolymphoid hyperplasia with eosinophilia: a study of 7 cases.

INTRODUCTION: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vasoproliferative disease of undetermined origin. It is characterized by the presence of nodular pseudo-tumors corresponding microscopically to a vascular proliferation within an inflammatory infiltrate made up of lymphocytes, macrophages, and eosinophils. The authors describe 7 cases of ALHE. METHODS: The 7 cases were diagnosed over a period of 19 years (1990-2008). Clinical data and histological slides were brought from the departments of dermatology and pathology of the Rabta Hospital. RESULTS: The 7 patients were 4 women and 3 men with an average age of 34.5 years. The cephalic localization was the most frequent. Lesions were solitary or multiple and formed papules or plaques of variable color. The diagnosis was based in all cases on histological findings. DISCUSSION: The main disease in the differential diagnosis of ALHE is Kimura disease, but the 2 entities have several clinical and histological differences. The pathogenesis remains unclear and there is no consensus on the best treatment.

Pemphigus vegetans: a clinical, histological, immunopathological and prognostic study.

BACKGROUND: Pemphigus vegetans (P Veg) is a rare clinical form of pemphigus. Studies on P Veg are rare in the literature and none has so far evaluated the prognostic parameters. OBJECTIVE: In this retrospective study of P Veg, we aimed to analyse epidemiological, clinical, immunopathological and therapeutic data. Study of prognostic factors with accuracy of patient survival was also carried out. METHODS: This is a retrospective study (1981-2009) including 17 cases of P Veg. Statistical analysis was performed with chi-square and Fisher tests looking for a possible relationship between clinical data and prognostic factors. Follow-up time and disease-free survival time were estimated using Kaplan-Meier methods. Clinical data were evaluated in univariate analysis looking for a significant association with survival. Equality of survival distribution was studied using log rank test. RESULTS: The hospital prevalence of P Veg was 0.084‰ with a frequency of 9.1% among pemphigus. The mean age at onset was 47.6 years, with a sex-ratio (F/M) about 4.66. Neumann P Veg was the predominant clinical form (11/17). Clinically, the lesions were multifocal (16/17), prevailed on folds and mucous membranes. Under corticosteroids the mean period for healing was 24 ± 9 days. During the follow-up time, three patients died and 11 patients relapsed. Median of overall relapse-free survival was 13 ± 1.7 months. No significant association between clinical data and prognostic factors was found. LIMITATIONS: This study was a retrospective chart analysis and the number of patients was small. CONCLUSION: The P Veg seems to be more frequent in Tunisia with high rate of mortality.

[Dermatofibrosarcoma protuberans in children]. / Dermatofibrosarcome protubérant de l'enfant.

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare skin neoplasm. Usually affecting adults, the incidence in children is even less frequent. Through a report of three pediatric cases of DFSP, we describe the particularities of this tumor in children. Three boys aged 8, 9, and 15 years presented with a firm nodular skin lesion of the trunk, varying in size from 1 to 5 cm. No previous trauma event had occurred. Diagnosis was confirmed in all cases by immunohistological study. Surgical excision was performed in all cases. No recurrence was evident during the follow-up period of, respectively, 15, 36, and 49 months. The DFSP is an infiltrative tumor of intermediate malignancy, with a limited potential for metastasis (<5%) but a high rate of local recurrence (≥ 50%). The incidence in children is even less frequent. In children, its seemingly benign clinical appearance may explain delays in diagnosis; the majority of lesions affect the extremities, suggesting a potential role-played by injury. In our observations, however, as in adults, the trunk was the site of occurrence. Despite the uncertain pathogenesis of this tumor, the finding of certain characteristic histopathological features helps establish an accurate diagnosis. As in adults, surgical treatment with large surgical margins remains the best practice for children with DFSP, directly affecting the prognosis.

Sweet's syndrome in a patient with rheumatoid arthritis, Sjögren's syndrome and lymph node tuberculosis.

Sweet's syndrome (SS) is an acute neutrophilic dermatosis characterised by abrupt onset of fever, leukocytosis and cutaneous eruption, with dermal neutrophilia on skin biopsy. Most cases are idiopathic but SS can be associated with various affections, especially neoplastic, inflammatory and infectious diseases. The authors report the case of an SS occurring in a patient with a known rheumatoid arthritis associated with a secondary Sjögren's syndrome, with incidental finding of concurrent lymph node tuberculosis. In case of SS, an associated disease (malignant, inflammatory or infectious diseases) must imperatively be searched for, knowing that two or more of these affections can coexist.